DESCRIPTION (provided by candidate): Primary insomnia is the most prevalent sleep disorder in the general population. Stressful life events have been proposed as major factors since insomniacs show alterations in stress hormone levels and, conversely, experimental insomnia can be induced by stress neuropeptides. Nevertheless, little is known about the central pathways underlying the effects of stress on the sleep-wake cycle. Activation of the ventrolateral preoptic nucleus (VLPO) is necessary to produce normal sleep, whereas during wakefulness the VLPO is strongly inhibited by inputs from wake-promoting areas. It has been proposed that the stability of the sleep-wake cycle depends on reciprocal inhibitory interactions between the VLPO and wake-promoting areas. Alterations of sleep architecture, such as those observed in insomnia, most likely involve changes in the neuronal activity of the sleep-wake circuitry. Animal models may be very useful to study the anatomical and functional relation between stress and sleep-wake circuits during insomnia. We propose to use acute exposure to a psychological stressor that causes transient insomnia as a simple model to study the basic functional changes elicited by stress on the sleep-wake circuitry. Our hypothesis is that insomnia is caused by decreased VLPO activity evoked by activation of specific inhibitory VLPO afferents that are stress-sensitive. The aims of this proposal are to determine whether: (1) specific VLPO afferents are activated during stress-induced insomnia, (2) they provide inhibitory inputs to VLPO, and (3), selective destruction of these afferents attenuates transient insomnia. Understanding the biological mechanisms underlying stress-induced transient insomnia will provide an essential framework for future studies of chronic insomnia and will help to identify targets for more specific pharmacological treatments. [unreadable] [unreadable]